The novel high-frequency variant of TRPV3 p.A628T in East Asians showing faster sensitization in response to chemical agonists

Choi, Seong Woo; Choi, Si Won; Chae, Jeesoo; Yoo, Hae Young; Kim, Jong‐Il; Kim, Sung Joon

doi:10.1007/s00424-019-02309-9

Cited by 2 publications

(2 citation statements)

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“…TRPV3 activity is critical to the structure of, and for the function of, skin [ 13 , 14 ], and both loss- and gain-of-function mutations in human TRPV3 are associated with skin diseases such as Olmsted syndrome [ 15 ] and focal palmoplantar keratoderma [ 16 ]. We recently reported a novel high-frequency variant of TRPV3 p. A628T in East Asians which showed a faster sensitization in response to chemical agonists [ 17 ]. In addition, since TRPV3 is implicated in skin inflammation and irritative pruritic sensation [ 8 ], the investigation of TRPV3 inhibitors is drawing attention for the treatment of cutaneous sensory disorders [ 6 , 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…The ion channels in keratinocytes, such as the transient receptor potential vanilloid (TRPV) family of cation channels and K + channels, are drawing attention regarding their roles in differentiation, sensation, and inflammatory responses [ 5 , 6 , 7 , 8 , 9 , 10 ]. Among the TRPV family channels, it is well known that TRPV3 is involved in the differentiation of keratinocytes and its pathologic activity or genetic mutations are associated with skin disorders such as Olmsted syndrome [ 6 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. In addition to TRPV3, the Ca 2+ -selective Orai1 channel is also known to play important roles in skin physiology and pathophysiology [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Multiple Effects of Echinochrome A on Selected Ion Channels Implicated in Skin Physiology

et al. 2023

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Echinochrome A (Ech A), a naphthoquinoid pigment from sea urchins, is known to have anti-inflammatory and analgesic effects that have been suggested to be mediated by antioxidant activity and intracellular signaling modulation. In addition to these mechanisms, the ion channels in keratinocytes, immune cells, and nociceptive neurons may be the target for the pharmacological effects. Here, using the patch clamp technique, we investigated the effects of Ech A on the Ca2+-permeable TRPV3, TRPV1 and Orai1 channels and the two-pore domain K+ (K2P) channels (TREK/TRAAK, TASK-1, and TRESK) overexpressed in HEK 293 cells. Ech A inhibited both the TRPV3 and Orai1 currents, with IC50 levels of 2.1 and 2.4 μM, respectively. The capsaicin-activated TRPV1 current was slightly augmented by Ech A. Ech A alone did not change the amplitude of the TREK-2 current (ITREK2), but pretreatments with Ech A markedly facilitated ITREK2 activation by 2-APB, arachidonic acid (AA), and acidic extracellular pH (pHe). Similar facilitation effects of Ech A on TREK-1 and TRAAK were observed when they were stimulated with 2-APB and AA, respectively. On the contrary, Ech A did not affect the TRESK and TASK-1 currents. Interestingly, the ITREK2 maximally activated by the combined application of 2-APB and Ech A was not inhibited by norfluoxetine but was still completely inhibited by ruthenium red. The selective loss of sensitivity to norfluoxetine suggested an altered molecular conformation of TREK-2 by Ech A. We conclude that the Ech A-induced inhibition of the Ca2+-permeable cation channels and the facilitation of the TREK/TRAAK K2P channels may underlie the analgesic and anti-inflammatory effects of Ech A.

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